Immunotherapy of patients with metastatic malignant melanoma using tumor infiltrating lymphocytes and interleukin-2 has resulted in significant clinical regressions. Our present studies are focused on the identification of lymphocytes infiltrating breast and ovarian carcinomas that have specific antitumor reactivity. Our goal is to translate these findings into therapies for patients with these diseases. l. Screening of breast cancer infiltrating lymphocytes and establishment of tumor lines. TIL from 54 breast cancer patients (primary or metastatic sites) have been screened for specific tumor reactivity. No culture has shown specific tumor lysis. Three cultures, however, have shown specific cytokine secretion when stimulated with fresh tumor. These cultures which are CD4 positive and MHC class II restricted, apparently recognize unique tumor antigens present in each of these 3 breast cancer patients. Attempts to culture breast cancer cells derived from these patients have been largely unsuccessful. In order to establish a renewable source of tumor, cryopreserved tumor cells derived from breast cancer patients have been implanted subcutaneously in BNX mice using matrigel and estrogen supplementation. This technique has resulted in successful tumor growth in approximately 50% of cases. The goal of this work is to use these biologic reagents to characterize the tumor antigens recognized by lymphocytes. These findings would have potential value in the development of vaccines and other immunotherapies. 2. Screening of ovarian cancer infiltrating lymphocytes. Lymphocytes derived from malignant ascites or from solid tumor metastases have been cultured from 13 patients. These lymphocytes were characterized for phenotype, cytotoxicity, and ability to secrete cytokines in response to autologous tumor stimulation. Lymphocyte cultures derived from four patients preferentially recognized autologous tumor as measured by cytokine secretion. These cultures were predominantly CD4 positive and MHC class II restricted. The goal of this work is to characterize the antigens recognized by ovarian cancer specific lymphocytes and use this information to develop new vaccines or immunotherapies.